LB18. An Enveloped Virus-like Particle (eVLP) Cytomegalovirus (CMV) Vaccine is Immunogenic and Safe: Results of a First-in-Humans Study
Session: Oral Abstract Session: Late Breaker Oral Abstracts: Influenza and Vaccines
Saturday, October 6, 2018: 11:10 AM
Room: S 152-154
Background: CMV is the most common cause of congenital infection and may result in permanent neurodevelopmental injury including vision and hearing loss. A vaccine to prevent transmission of CMV during pregnancy or to immunocompromised persons is a public health priority. Neutralizing antibodies (nAb) to the CMV envelope glycoprotein B(gB) in natural infection are thought to confer protection, but some vaccine candidates based on this protein alone have been insufficiently immunogenic. In this FiH dose-ranging, controlled, observer-blinded study the safety and immunogenicity of an eVLP expressing the ectodomain of gB fused to transmembrane and cytoplasmic domains of the vesicular stomatitis virus G protein (gB-G) was evaluated.

Method: Healthy CMV-seronegative 18-40 year olds at 3 sites in Canada (Vancouver, Montreal, Halifax) were randomized to one of 4 dose formulations (0.5µg, 1µg, or 2µg gB content with Alum) or 1µg gB without Alum, or placebo given on days 0, 56 and 168. Outcome measures were solicited and unsolicited adverse events (AE), severe AE, gB binding antibody titers and avidity assessment, and nAb to CMV infection of fibroblast and epithelial cells. A Data Safety Monitoring Board was in place.

Result: Among 128 participants, the most common solicited local and general AEs were pain and headache, respectively. No SAEs or withdrawals occurred. A dose-dependent boosting of nAb titers was observed after doses 2 and 3, with the highest titers in the Alum-adjuvanted 2.0 µg dose recipients. Fibroblast cell nAb were seen in 100% of 2.0 µg dose recipients, and epithelial cell nAb in 31%. Epithelial cell nAb was correlated with higher geometric mean gB binding titers, and there was a correlation between fibroblast and epithelial cell nAb titers.

Conclusion: An eVLP CMV vaccine was immunogenic at very low doses in healthy seronegative adults and no safety signals were seen. Alum adjuvantation increased immunogenicity as did higher antigen content and multiple doses. This phase 1 trial supports further development of this eVLP CMV vaccine candidate.

ClinicalTrials.gov NCT02826798

Soren Gantt, MD, PhD1, Caroline Quach, MD, MSc, FRCPC, FSHEA2,3, David E Anderson, PhD4, Francisco Diaz-Mitoma, MD, PhD4 and Joanne Langley, MD5, (1)Pediatric, Infectious Diseases, University of British Columbia, Vancouver, BC, Canada, (2)Infection Prevention & Control, Laboratory Medicine, CHU Sainte-Justine, Montreal, QC, Canada, (3)Microbiology, Infectious Diseases & Immunology, University of Montreal, Montreal, QC, Canada, (4)VBI Vaccines, Cambridge, MA, (5)Pediatric Infectious Diseases, Dalhousie University, Halifax, NS, Canada

Disclosures:

S. Gantt, VBI Vaccines: Investigator , No direct financial benefit-- company provided institutional support for clinical trial .

C. Quach, VBI Vaccines: Investigator , No direct financial benefit-- company provided institutional support for clinical trial .

D. E. Anderson, VBI Vaccines: Employee and Shareholder , Salary .

F. Diaz-Mitoma, VBI Vaccines: Consultant and Shareholder , Salary .

J. Langley, VBI Vaccines: Investigator , No direct financial benefit-- company provided institutional support for clinical trial .

Findings in the abstracts are embargoed until 12:01 a.m. PDT, Wednesday Oct. 3rd with the exception of research findings presented at the IDWeek press conferences.